Benign Prostatic Hyperplasia (BPH)

Benign prostatic hyperplasia (BPH) is characterized by proliferation of the cellular elements of the prostate resulting in enlargement of the prostate gland that may restrict the flow of urine from the bladder. BPH is considered a normal part of the aging process in men and an estimated 50% of men demonstrate histo-pathologic BPH by age 60 years. This number increases to 90% by age 85 years.

The voiding dysfunction that results from prostate gland enlargement and bladder outlet obstruction (BOO) is termed as lower urinary tract symptoms (LUTS). Approximately half of men diagnosed with histo-pathologic BPH demonstrate moderate-to-severe LUTS. Prostate volume may increase over time in men with BPH. In addition, peak urinary flow, voided volume, and symptoms may worsen over time in men with untreated BPH. The risk of urinary retention and the need for corrective surgery increases with age.

The prostate gland is a chestnut-shaped reproductive organ located directly beneath the bladder in the male, which adds secretions to the sperm during the ejaculation of semen. The gland surrounds the urethra, the duct that serves for the passage of both urine and semen; rounded at the top, the gland narrows to form a blunt point at the bottom, or apex. The diameter in the broadest area is about 4 cm (1.6 inches). The two ejaculatory ducts, which carry sperm and the fluid secreted by the seminal vesicles, converge and narrow in the centre of the prostate and unite with the urethra; the urethra then continues to the lower segment of the prostate and exits near the apex.

The prostate gland is a conglomerate of 30 to 50 tubular or saclike glands that secrete fluids into the urethra and ejaculatory ducts. The secretory ducts and glands are lined with a moist, folded mucous membrane. The folds permit the tissue to expand while storing fluids. Beneath this layer is connective tissue composed of a thick network of elastic fibres and blood vessels. The tissue that surrounds the secretory ducts and glands is known as interstitial tissue; this contains muscle, elastic fibres, and collagen fibres that give the prostate gland support and firmness. The capsule enclosing the prostate is also of interstitial tissue.

In man, the prostate contributes 15–30 percent of the seminal plasma (or semen) secreted by the male. The fluid from the prostate is clear and slightly acidic. It is composed of several protein-splitting enzymes; fibrolysin, an enzyme that reduces blood and tissue fibres; citric acid and acid phosphatase, which help to increase the acidity; and other constituents, including ions and compounds of sodium, zinc, calcium, and potassium.

Normally the prostate reaches its mature size at puberty, between the ages of 10 and 14. Around the age of 50, the size of the prostate and the amount of its secretions commonly decrease. Increase in size after midlife, often making urination difficult, may occur as a result of inflammation or malignancy.

Symptoms of BPH can be caused by other disease processes. A history and a physical examination are required in ruling out other etiologies of urinary tract symptom (LUTS). When the prostate enlarges, it may act like a "clamp on a hose," constricting the flow of urine and causing the following common symptoms:

Urinary frequency - The need to urinate frequently during the day or night (nocturia), usually voiding only small amounts of urine with each episode

Urinary urgency - The sudden, urgent need to urinate, owing to the sensation of imminent loss of urine without control

Incomplete bladder emptying - The feeling of persistent residual urine, regardless of the frequency of urination

Straining - The need to strain or push to initiate and maintain urination in order to more fully evacuate the bladder

Decreased force of stream - The subjective loss of force of the urinary stream over time

Dribbling - The loss of small amounts of urine due to a poor urinary stream.

International Prostate Symptom Score (IPSS)The severity of BPH can be determined with the International Prostate Symptom Score (IPSS). Questions concern incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Based on the sum of the score for all 8 questions, patients are classified as 0-7 (mildly symptomatic), 8-19 (moderately symptomatic), or 20-35 (severely symptomatic).

International prostate symptom score (IPSS)

Name:

Date:

Not at all

Less than 1 time in 5

Less than half the time

About half the time

More than half the time

Almost always

Your score

Incomplete emptying Over the past month, how often have you had a sensation of not emptying your bladder completely after you finish urinating?

0

1

2

3

4

5

Frequency

Over the past month, how often have you had to urinate again less than two hours after you finished urinating?

0

1

2

3

4

5

Intermittency

Over the past month, how often have you found you stopped and started again several times when you urinated?

0

1

2

3

4

5

Urgency

Over the last month, how difficult have you found it to postpone urination?

0

1

2

3

4

5

Weak stream

Over the past month, how often have you had a weak urinary stream?

0

1

2

3

4

5

Straining

Over the past month, how often have you had to push or strain to begin urination?

0

1

2

3

4

5

None

1 time

2 times

3 times

4 times

5 times or more

Your score

NocturiaOver the past month, many times did you most typically get up to urinate from the time you went to bed until the time you got up in the morning?

0

1

2

3

4

5

Total IPSS score

Quality of life due to urinary symptoms

Delighted

Pleased

Mostly satisfied

Mixed – about equally satisfied and dissatisfied

Mostly dissatisfied

Unhappy

Terrible

If you were to spend the rest of your life with your urinary condition the way it is now, how would you feel about that?

Digital rectal examination (DRE) is an integral part of the evaluation in men with presumed BPH. During this portion of the examination, prostate size and contour can be assessed, nodules can be evaluated, and areas suggestive of malignancy can be detected. The normal prostate volume in a young man is approximately 20 g. A more precise volumetric determination can be made using transrectal ultrasonography (TRUS) of the prostate.

Decreased anal sphincter tone or the lack of a bulbocavernosus muscle reflex may indicate an underlying neurological disorder.

ComplicationsComplications related to bladder outlet obstruction (BOO) secondary to BPH include the following:

Urinary retention

Recurrent urinary tract infections

Gross hematuria

Bladder calculi

Renal failure or uremia

UrinalysisExamine the urine using dipstick methods and/or via centrifuged sediment evaluation to assess for the presence of blood, leukocytes, bacteria, protein, or glucose.

Urine CultureThis may be useful to exclude infectious causes of irritative voiding and is usually performed if the initial urinalysis findings indicate an abnormality.

Prostate-Specific Antigen (PSA) Although BPH does not cause prostate cancer, men at risk for BPH are also at risk for prostate cancer and should be screened accordingly. Notably, men with larger prostates may have slightly higher PSA levels.

Electrolytes, CreatinineThese evaluations are useful screening tools for chronic renal insufficiency in patients who have high postvoid residual (PVR) urine volumes. A routine serum creatinine measurement is not indicated in the initial evaluation of men with lower urinary tract symptoms (LUTS) secondary to BPH.

UltrasonographyUltrasonography (abdominal, renal, transrectal) is useful in determining bladder and prostate size and the degree of hydronephrosis in patients with urinary retention or signs of renal insufficiency. Generally, they are not indicated for the initial evaluation of uncomplicated LUTS.

Transrectal ultrasonography (TRUS) of the prostate is recommended in selected patients, to determine the dimensions and volume of the prostate gland. The success of certain minimally invasive treatments may depend on the anatomical characteristics of the gland. In patients with elevated PSA levels, TRUS-guided biopsy may be indicated.

Imaging of the upper tracts is indicated in patients who present with concomitant hematuria, a history of urolithiasis, an elevated creatinine level, high PVR volume, or history of upper urinary tract infection.

Optional tests

Flow rate is useful in the initial assessment and to help determine the response to treatment. It may be performed prior to embarking on any active treatments, including medical treatment. A maximal flow rate (Qmax) is the single best measurement, but a low Qmax does not help differentiate between obstruction and poor bladder contractility. For more detailed analysis, a pressure flow study (urodynamic testing) is required. A Qmax value of greater than 15 ml/s is considered by many to be normal. A value of less than 7 ml/s is widely accepted as low.

Postvoid residual urine in order to gauge the severity of bladder decompensation. It can be obtained invasively with a catheter or noninvasively with a transabdominal ultrasonic scanner. A high PVR (ie, 350 ml) may indicate bladder dysfunction and/or bladder outlet obstruction and may predict a poor response to treatment.

Cytologic examination of the urine may be considered in patients with predominantly irritative voiding symptoms.

Endoscopy of the Lower Urinary Tract Cystoscopy may be indicated in patients scheduled for invasive treatment or in whom a foreign body or malignancy is suspected. In addition, endoscopy may be indicated in patients with a history of sexually transmitted disease (eg, gonococcal urethritis), prolonged catheterization, or trauma. Findings may suggest urethral stricture as the cause of BOO, instead of BPH. Flexible cystoscopy can be easily performed in several minutes in an office-based setting using topical gel-based intraurethral anesthesia without sedation.

Patients with mild symptoms (IPSS < 7) or moderate-to-severe symptoms (IPSS ≥8) of benign prostatic hyperplasia (BPH) who are not bothered by their symptoms and are not experiencing complications of BPH should be managed with a strategy of watchful waiting. In these situations, medical therapy is not likely to improve their symptoms and/or quality of life. In addition, the risks of treatment may outweigh any benefits. Patients managed expectantly with watchful waiting are usually re-examined annually.

The era of medical therapy for BPH dawned in the mid 1970s with the use of nonselective alpha-blockers such as phenoxybenzamine. The medical therapeutic options for BPH have evolved significantly over the last 3 decades, giving rise to the receptor-specific alpha-blockers that comprise the first line of therapy.

MedicationsThe goals of pharmacotherapy for benign prostatic hypertrophy (BPH) are to reduce morbidity and to prevent complications. The agents used include alpha-adrenergic blockers, 5-alpha-reductase inhibitors, and various combinations.

Alpha-Adrenergic Blockers

A significant component of LUTS secondary to BPH is believed to be related to the smooth-muscle tension in the prostate stroma, urethra, and bladder neck. The smooth-muscle tension is mediated by the alpha-1-adrenergic receptors; therefore, alpha-adrenergic receptor–blocking agents should theoretically decrease resistance along the bladder neck, prostate, and urethra by relaxing the smooth muscle and allowing passage of urine.

Alfuzosin Alfuzosin is indicated for the treatment of the signs and symptoms of BPH. Alfuzosin is an alpha-1 blocker of adrenoreceptors in the prostate. Blockade of adrenoreceptors may cause smooth muscles in the bladder neck and prostate to relax, resulting in improvement in urine flow rate and reduction in symptoms of BPH.

Terazosin Terazosin is a quinazoline compound that counteracts alpha1-induced adrenergic contractions of bladder neck, facilitating urinary flow in the presence of BPH. It is indicated for the treatment of symptomatic BPH and hypertension. Its effect on voiding symptoms and flow rates is dose-dependent. It improves irritative and obstructive voiding symptoms. Improvement in flow rate is objective. A Hytrin starter pack is available for easy dosing progression to 5 mg.

Doxazosin Doxazosin is indicated for the treatment of urinary outflow obstruction and irritative symptoms associated with BPH and hypertension. It inhibits postsynaptic alpha-adrenergic receptors, resulting in vasodilation of veins and arterioles and a decrease in total peripheral resistance and blood pressure. It is a long-acting alpha1-blocking agent with a profile similar to that of terazosin. Doxazosin improves irritative and obstructive voiding symptoms.

Tamsulosin Tamsulosin is indicated for the treatment of the signs and symptoms of BPH. It is an alpha-adrenergic blocker specifically targeted to alpha-1 receptors. Tamsulosin has the advantage of producing relatively less orthostatic hypotension; it requires no gradual up-titration from the initial dosage. It inhibits postsynaptic alpha-adrenergic receptors, resulting in vasodilation of veins and arterioles and a decrease in total peripheral resistance and blood pressure. It improves irritative and obstructive voiding symptoms.

Silodosin Silodosin is indicated for the treatment of the signs and symptoms of BPH. Silodosin selectively antagonizes postsynaptic alpha1-adrenergic receptors in the prostate, bladder base, prostatic capsule, and prostatic urethra. This action induces smooth muscle relaxation and improves urine flow.

5-Alpha-Reductase Inhibitors

These agents are used to treat symptomatic BPH in men with an enlarged prostate. They inhibit the conversion of testosterone to DHT, causing DHT levels to drop, which, in turn, may decrease prostate size.

Finasteride Finasteride is indicated for the treatment of symptomatic BPH in men with an enlarged prostate. When combined with doxazosin, it can also reduce the risk of symptomatic progression of BPH. Finasteride inhibits conversion of testosterone to DHT, causing serum DHT levels to decrease. It is beneficial in men with prostates larger than 40 g and can improve symptoms and reduce prostatic size by 20-30%. Reduction in prostate size is sustained for 5 years following treatment. Finasteride improves urinary flow rate by 2 mL/s.

Dutasteride Dutasteride is indicated for the treatment of BPH as monotherapy or in combination with tamsulosin. Dutasteride improves symptoms, reduces urinary retention, and may decrease the need for BPH-related surgery. It inhibits 5alpha-reductase isoenzymes types I and II. This agent suppresses conversion of testosterone to DHT by more than 95%, causing serum DHT levels to decrease.

Combination Products

Dutasteride and tamsulosin The combination of dutasteride, a 5-alpha-reductase inhibitor, and tamsulosin, an alpha-adrenergic antagonist is indicated for benign prostatic hypertrophy in men with an enlarged prostate. Each cap contains dutasteride 0.5 mg and tamsulosin 0.4 mg.

SurgeryThe indications to proceed with a surgical intervention include the following:

Transurethral Resection of Prostate (TURP) TURP is an operation for relieving Bladder Outlet Obstruction (BOO). It allows urine to flow freely thus reducing the symptom of BPH. TURP is performed with regional or general anesthesia and involves the placement of a working sheath in the urethra through which a hand-held device with an attached wire loop is placed. High-energy electrical cutting current is run through the loop shave away prostatic tissue. The entire device is usually attached to a video camera to provide vision for the surgeon.

The main disadvantage of TURP is that TURP carries a significant risk of morbidity (18%) and mortality (0.23%). More recent techniques using bipolar cautery resection devices have lowered the morbidity associated with TURP.

Open Prostatectomy This procedure is used in the following cases:

Patients with very large prostates (>100 g)

Patients with concomitant bladder stones or bladder diverticula

Patients who cannot be positioned for transurethral surgery.

Open prostatectomy requires hospitalization and involves the use of general/regional anesthesia and a lower abdominal incision. The inner core of the prostate (adenoma), which represents the transition zone, is shelled out, thus leaving the peripheral zone behind. Open prostatectomy usually has an excellent outcome in terms of improvement of urinary flow and urinary symptoms. Disadvantages of open prostatectomy may include significant blood loss, resulting in transfusion.

Minimally Invasive Treatment

There is considerable interest in the development of other therapies to decrease the amount of obstructing prostate tissue while avoiding the adverse effects associated with TURP. These therapies are collectively called minimally invasive therapies which include:

TUIP

Transurethral Incision of the Prostate Transurethral incision of the prostate (TUIP) has been in use for many years and, for a long time, was the only alternative to TURP. It may be performed with local anesthesia and sedation. TUIP is suitable for patients with small prostates and for patients unlikely to tolerate TURP well because of other medical conditions. TUIP is associated with less bleeding and fluid absorption than TURP. It is also associated with a lower incidence of retrograde ejaculation and impotence than TURP.

Lasers

Lasers deliver heat to the prostate causing tissue death by coagulative necrosis, with subsequent tissue contraction; however, laser coagulation of the prostate in this specific sense has met with limited results. Lasers have been used to directly evaporate, or to melt away, prostate tissue, which is more effective than laser coagulation. Laser techniques include:

Photoselective vaporization of the prostate produces a beam that delivers heat energy into the prostate, resulting in destruction/ablation of the prostate tissue.

Potassium-titanyl-phosphate (KTP) and holmium lasers are used to cut and/or enucleate the prostate, similar to the TURP technique. These are widely used laser techniques.

Transurethral vaporization/ablation with the KTP or holmium laser can be performed with general or spinal anesthesia and can be performed in an outpatient setting. Catheter time usually lasts less than 24 hours. Studies suggest that photoselective vaporization of the prostate can significantly improve and sustain symptomatic and urodynamic outcomes.

Lasers may be used in a knifelike fashion to directly cut away prostate tissue (ie, holmium laser enucleation of the prostate), similar to a TURP procedure. The holmium laser allows for simultaneous cutting and coagulation, making it quite useful for prostate resection. Laser enucleation of the prostate has proved to be safe and effective for treatment of symptomatic BPH, regardless of prostate size, with low morbidity and short hospital stay.

Laser treatment usually results in decreased bleeding, fluid absorption, and length of hospital stay, as well as decreased incidence of impotence and retrograde ejaculation when compared with standard TURP. Disadvantages of laser:

Healing from laser treatment does not occur until after a period when dead cells slough; thus, patients may experience urinary urgency or irritation, resulting in frequent or uncomfortable urination for a few weeks.

The results of laser therapy vary from one another because not all wavelengths yield the same tissue effects.

Long-term Monitoring Patients with BPH who have symptoms significant enough to be placed on medication should be evaluated during office visits to discuss the efficacy of the medication and potential dose adjustment. These visits should take place at least biannually. Patients should undergo Digital rectal examination (DRE) and Prostate-Specific Antigen (PSA) screening at least annually.